This research program is designed to (a) characterize and quantitate the functional components of the normal and altered surfactant system and (b) to provide answers directly relating to the mechanisms as well as prenatal diagnosis and treatment of hyaline membrane disease of the newborn (HMD) and other pathological conditions of the neonatal lung. For this purpose we have developed reliable and rapid methods for the isolation and purification of intracellular and alveolar surfactant as well as surfactant contaminated with plasma proteins. These methods will be used for the evaluation of surfactant changes in amniotic fluid, tracheal aspirates of newborns treated for respiratory distress and lungs obtained at autopsy from fetuses as well as newborns with or without HMD. The above human studies are complemented with selected animal experiments using suitable models developed in our laboratory and appropriate structural, functional and biochemical parameters in order to investigate the pathophysiology of perinatal surfactant biosynthesis and secretion and to evaluate the role of in utero alveolar injury and repair in postnatally manifested surfactant deficiency.